Gluttonous Male Mice Give Diabetes to Daughters

A prospective dad’s diet may affect the health of his future children, suggests a study of cross-generational nutritional impacts in mice.

Males were fed a high-fat diet, becoming obese and diabetic, then mated with lean, healthy females. At six weeks of age, or the mouse equivalent of puberty, their daughters became glucose-intolerant, a major step toward diabetes.

That overweight moms are more likely to have overweight babies is known, but the phenomenon hadn’t before been demonstrated in males of any species.

“It is difficult to comment on how relevant our finding might be for the current diabetes epidemic, but our data suggest that a father’s diet, or the fact that he is obese or diabetic, may influence his offspring’s risk of disease,” said neuropharmacologist Margaret Morris of Australia’s University of New South Wales.

It’s still too soon to extrapolate to humans the rodent results of Morris and her colleagues, which were published October 20 in Nature. But the results fit an emerging understanding of the role of epigenetics, or the chemical code that turns genes on and off, allowing on-the-fly adaptation to changing environmental conditions.

Epigenetic changes take place during an individual’s lifetime, but they can be passed down to children and even grandchildren. That was famously described in 1998, in a long-term study of Dutch children born during the World War II famine, and epigenetic research has expanded rapidly in the last decade.

Also expanding is America’s waistline, with type 2 diabetes — the kind triggered by a poor diet and lack of activity — reaching epidemic levels.

“The dramatic increase in human metabolic disorders such as obesity and diabetes warrants considering the influence of environmental factors on the germ line,” wrote Michael Skinner, a Washington State University reproductive biologist, in a commentary accompanying the findings.

A family history of diabetes is a reliable indicator of increased disease risk. This is usually interpreted purely in terms of genetic mutations, rather than epigenetic changes.

In Morris’ study, however, it all fit together. When she compared gene-expression patterns in the sperm of diabetic male mice to healthy males, she found tweaks in hundreds of genes linked to activity in the pancreas, which produces the blood-sugar-regulating hormone insulin.

The males’ high-fat diet had caused pervasive cellular changes, which were then passed to their daughters. Most disturbingly, the daughters developed metabolic malfunction even when they were fed a healthy diet.

According to Morris, as-yet-unpublished research suggests that sons were similarly affected.

Morris next plans to study how the daughters’ inherited metabolic malfunction progresses with age, and whether it’s passed to their offspring as well.